| Size | Price | Stock | Qty |
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| 1mg |
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| 10mg | |||
| 25mg | |||
| 50mg | |||
| Other Sizes |
| Targets |
Neuropeptide Y (NPY) Y4 receptor (primary) and Y5 receptor (secondary). Ki for human Y4 receptor is 0.056 nM. EC₅0 values are 87.1 pM (human Y4) and 36.3 pM (rat Y4).
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| ln Vitro |
One such peptide is human pancreatic polypeptide (hPP), which is released from the pancreatic islets' F cells in response to circadian cycles, food intake, and calorie load following meals. This 36-amino acid peptide is amidated at the C-terminus and has a distinctive hairpin-like pancreatic polypeptide (PP) structure. It operates on the Y4 receptor to cause satiety and to postpone the emptying of the stomach and the motility of the stomach [1]. Human pancreatic polypeptide (hPP) (10 nM-1 μM) was added, and the baseline and stimulated release significantly decreased in a dose-dependent manner. Human pancreatic polypeptide (hPP) has the ability to block both stimulated and basal production of neuropeptide Y (NPY), and its pharmacological properties point to the involvement of Y4 presynaptic receptors [2].
In vitro, human pancreatic polypeptide binds to NPY Y4 receptors with high affinity (Ki = 0.056 nM). It reduces forskolin-induced cAMP accumulation in L-M(TK-) cells recombinantly expressing human and rat Y4 receptors (EC₅0 = 87.1 and 36.3 pM, respectively). Addition of hPP (10 nM-1 microM) results in significant, dose-dependent reduction in both basal and stimulated neuropeptide release. hPP also inhibits basal and stimulated NPY release with a pharmacological profile suggesting a role for Y4 presynaptic receptors. The peptide adopts a characteristic hairpin-like pancreatic polypeptide (PP)-fold structure. |
| ln Vivo |
In vivo, human pancreatic polypeptide acts at the Y4 receptor to induce satiety, delay gastric emptying, and reduce food intake. It is involved in the regulation of gastrointestinal function and energy homeostasis. The peptide is released in response to food consumption and plays a role in the feedback regulation of pancreatic secretion. PEGylated forms of hPP have been shown to improve stability and reduce food intake in mouse models.
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| Enzyme Assay |
Receptor binding assays are performed using membrane preparations from cells expressing recombinant human NPY Y4 receptors (e.g., L-M(TK-) cells). Membranes are incubated with radiolabeled [¹2⁵I]-pancreatic polypeptide (20-50 pM) and increasing concentrations of unlabeled human pancreatic polypeptide (0.001-1000 nM) in binding buffer (25 mM HEPES, pH 7.4, containing 2.5 mM CaCl2, 1 mM MgCl2, 0.1% BSA, and protease inhibitors) at room temperature for 2 hours. Non-specific binding is determined in the presence of 1 microM unlabeled peptide. Bound ligand is separated by rapid filtration through GF/C filters pre-soaked in 0.3% polyethyleneimine. Radioactivity is counted and Ki values are calculated from competitive binding curves using non-linear regression.
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| Cell Assay |
Functional assays are conducted in cells recombinantly expressing NPY Y4 receptors (e.g., L-M(TK-) cells). Cells are seeded in 96-well plates and pre-incubated with forskolin (1-5 microM) to stimulate cAMP production. Human pancreatic polypeptide is added at concentrations ranging from 0.001 nM to 1 microM and incubated for 15-30 minutes at 37degC. Intracellular cAMP levels are measured using competitive ELISA or HTRF-based cAMP detection kits. Inhibition of cAMP accumulation is expressed as percentage of forskolin-stimulated control. EC₅0 values are calculated from dose-response curves. For calcium mobilization assays, cells are loaded with calcium-sensitive dyes and receptor activation is measured by fluorescence changes.
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| Animal Protocol |
In vivo studies involve administration of human pancreatic polypeptide to rodents via intraperitoneal (IP) or intravenous (IV) routes. Doses typically range from 10-100 microg/kg. Food intake is monitored at multiple time points (1, 2, 4, 6, 24 hours) post-administration. Gastric emptying is assessed using the phenol red method or by measuring the retention of a test meal. For pharmacokinetic studies, blood samples are collected and plasma peptide concentrations are measured by radioimmunoassay or ELISA. The peptide's effects on gastrointestinal motility and pancreatic secretion are evaluated in anesthetized or conscious animal models.
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| ADME/Pharmacokinetics |
Human pancreatic polypeptide (hPP) has a short plasma half-life due to rapid proteolytic degradation. PEGylation at position 22 has been shown to improve stability and extend the half-life of the peptide in mice. The peptide is administered parenterally as it is not orally bioavailable. Distribution is consistent with other neuropeptides, with binding to Y4 receptors in the gastrointestinal tract and central nervous system. Elimination occurs primarily via enzymatic degradation and renal clearance. The peptide is stored as a lyophilized powder at -20degC to -80degC for long-term stability.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for human pancreatic polypeptide. As an endogenous peptide, it is generally well-tolerated at physiological and pharmacological doses. High doses may cause gastrointestinal effects such as reduced motility or altered secretion due to Y4 receptor activation. The peptide is for research use only and not for human therapeutic use. Standard safety precautions for handling peptides should be observed.
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| References |
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| Additional Infomation |
Pancreatic polypeptide (PP) is a pancreatic hormone composed of 36 amino acids, primarily secreted by endocrine cells located in the periphery of the islets of Langerhans, adjacent to somatostatin and glucagon-secreting cells. Peripherally administered pancreatic polypeptide can inhibit gastric acid secretion, gastric emptying, pancreatic enzyme secretion, and appetite. Pancreatic polypeptide deficiency in rats and mice is associated with obesity.
Human pancreatic polypeptide is an endogenous peptide hormone and research tool for studying NPY receptor pharmacology and gastrointestinal function. It serves as a valuable probe for Y4 receptor signaling, satiety regulation, and energy homeostasis. The peptide's sequence is Ala-Pro-Leu-Glu-Pro-Val-Tyr-Pro-Gly-Asp-Asn-Ala-Thr-Pro-Glu-Gln-Met-Ala-Gln-Tyr-Ala-Ala-Asp-Leu-Arg-Arg-Tyr-Ile-Asn-Met-Leu-Thr-Arg-Pro-Arg-Tyr-NH2. Molecular formula is C1₈₅H2₈₇N₅3O₅4S2 with MW 4181.71. Pancreatic polypeptide is not an approved therapeutic agent but is used in research to develop peptide-based therapies for obesity and metabolic disorders. |
| Molecular Formula |
C185H287N53O54S2
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|---|---|
| Molecular Weight |
4181.71097999997
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| Exact Mass |
4180.081
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| CAS # |
75976-10-2
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| Related CAS # |
59763-91-6
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| PubChem CID |
24868176
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| Appearance |
White to off-white solid powder
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| LogP |
-11.6
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| Hydrogen Bond Donor Count |
58
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| Hydrogen Bond Acceptor Count |
61
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| Rotatable Bond Count |
131
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| Heavy Atom Count |
294
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| Complexity |
10300
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| Defined Atom Stereocenter Count |
38
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| SMILES |
CCC(C)C(C(=O)NC(CC(=O)N)C(=O)NC(CCSC)C(=O)NC(CC(C)C)C(=O)NC(C(C)O)C(=O)NC(CCCNC(=N)N)C(=O)N1CCCC1C(=O)NC(CCCNC(=N)N)C(=O)NC(CC2=CC=C(C=C2)O)C(=O)N)NC(=O)C(CC3=CC=C(C=C3)O)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCCNC(=N)N)NC(=O)C(CC(C)C)NC(=O)C(CC(=O)O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CC4=CC=C(C=C4)O)NC(=O)C(CCC(=O)N)NC(=O)C(C)NC(=O)C(CCSC)NC(=O)C(CCC(=O)N)NC(=O)C(CCC(=O)O)NC(=O)C5CCCN5C(=O)C(C(C)O)NC(=O)C(C)NC(=O)C(CC(=O)N)NC(=O)C(CC(=O)O)NC(=O)CNC(=O)C6CCCN6C(=O)C(CC7=CC=C(C=C7)O)NC(=O)C(C(C)C)NC(=O)C8CCCN8C(=O)C(CCC(=O)O)NC(=O)C(CC(C)C)NC(=O)C9CCCN9C(=O)C(C)N
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| InChi Key |
HFDKKNHCYWNNNQ-YOGANYHLSA-N
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| InChi Code |
InChI=1S/C185H287N53O54S2/c1-20-92(10)144(175(286)228-125(84-137(190)248)164(275)215-115(64-75-294-19)159(270)222-121(78-90(6)7)167(278)232-145(98(16)239)176(287)219-116(33-24-68-203-185(198)199)178(289)236-71-27-36-131(236)170(281)216-110(32-23-67-202-184(196)197)154(265)220-118(147(191)258)79-100-39-47-104(241)48-40-100)231-168(279)123(81-102-43-51-106(243)52-44-102)225-155(266)109(31-22-66-201-183(194)195)211-153(264)108(30-21-65-200-182(192)193)212-162(273)119(76-88(2)3)223-166(277)127(86-142(256)257)221-150(261)95(13)205-148(259)94(12)207-160(271)122(80-101-41-49-105(242)50-42-101)224-158(269)111(55-59-134(187)245)210-149(260)96(14)206-152(263)114(63-74-293-18)214-156(267)112(56-60-135(188)246)213-157(268)113(57-61-139(250)251)217-171(282)132-37-29-73-238(132)181(292)146(99(17)240)233-151(262)97(15)208-161(272)124(83-136(189)247)226-165(276)126(85-141(254)255)209-138(249)87-204-169(280)129-34-25-70-235(129)180(291)128(82-103-45-53-107(244)54-46-103)229-174(285)143(91(8)9)230-173(284)133-38-28-72-237(133)179(290)117(58-62-140(252)253)218-163(274)120(77-89(4)5)227-172(283)130-35-26-69-234(130)177(288)93(11)186/h39-54,88-99,108-133,143-146,239-244H,20-38,55-87,186H2,1-19H3,(H2,187,245)(H2,188,246)(H2,189,247)(H2,190,248)(H2,191,258)(H,204,280)(H,205,259)(H,206,263)(H,207,271)(H,208,272)(H,209,249)(H,210,260)(H,211,264)(H,212,273)(H,213,268)(H,214,267)(H,215,275)(H,216,281)(H,217,282)(H,218,274)(H,219,287)(H,220,265)(H,221,261)(H,222,270)(H,223,277)(H,224,269)(H,225,266)(H,226,276)(H,227,283)(H,228,286)(H,229,285)(H,230,284)(H,231,279)(H,232,278)(H,233,262)(H,250,251)(H,252,253)(H,254,255)(H,256,257)(H4,192,193,200)(H4,194,195,201)(H4,196,197,202)(H4,198,199,203)/t92-,93-,94-,95-,96-,97-,98+,99+,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,127-,128-,129-,130-,131-,132-,133-,143-,144-,145-,146-/m0/s1
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| Chemical Name |
(4S)-5-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-aminopropanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-3-carboxypropanoyl]amino]-4-oxobutanoyl]amino]propanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~5.98 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (0.60 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (0.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2391 mL | 1.1957 mL | 2.3914 mL | |
| 5 mM | 0.0478 mL | 0.2391 mL | 0.4783 mL | |
| 10 mM | 0.0239 mL | 0.1196 mL | 0.2391 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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